Karger Publishers, Acta Haematologica, 4(133), p. 354-364, 2015
DOI: 10.1159/000369446
Full text: Unavailable
<b><i>Background/Aims:</i></b> We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients. <b><i>Methods:</i></b> Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR. <b><i>Results:</i></b> Anti-apoptotic genes <i>(c-FLIP </i>and<i> MCL-1)</i> were overexpressed and the pro-apoptotic <i>BIK </i>was reduced in CML patients. Expression of <i>BMF, A1, c-FLIP, MCL-1, CIAP-2 </i>and <i>CIAP-1 </i>was modulated by DAS. In IM-resistant patients, expression of <i>A1, c-FLIP, CIAP-1</i> and <i>MCL-1 </i>was upregulated, and <i>BCL-2</i>,<i> CIAP-2</i>,<i> BAK, BAX, BIK </i>and <i>FASL </i>expression was downregulated. <b><i>Conclusion:</i></b> Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM.